H2O2 induces translocation of APE/Ref-1 to mitochondria in the Raji B-cell line
H2O2 induces translocation of APE/Ref-1 to mitochondria in the Raji B-cell line
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DOI：
10.1002/jcp.10159
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发表时间：
2002-11-01
影响因子：
5.6
通讯作者：
Pucillo, C
中科院分区：
文献类型：
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作者：
Frossi, B;Tell, G;Pucillo, C
活性氧 (ROS) 作为呼吸副产品产生，并用作外-内信号通路中的信号转导中间体。炎症反应期间也会产生 ROS，并且已证明过氧化氢可能触发 B 淋巴细胞的激活，类似于表面免疫球蛋白的交联。另一方面，外源和内源产生的 ROS 都是核和线粒体 DNA (mtDNA) 损伤的主要来源。碱基切除修复 (BER) 酶 APE/Ref-1 通常修复小的核 DNA 损伤，例如氧化或烷基化碱基。但尚不清楚线粒体中是否也存在能够消除核 DNA 氧化损伤的 DNA 修复机制。在这里，我们通过共聚焦显微镜和蛋白质印迹分析表明，在 B 淋巴细胞 Raji 细胞系中，H2O2 激活后，APE/Ref-1 的一部分迅速重新定位到线粒体中。 APE/Ref-1 靶向线粒体与细胞色素 c 丢失或细胞凋亡诱导无关。这些发现表明，APE/Ref-1 易位至线粒体以应对氧化应激，从而可能发挥保护功能。 (C) 2002 Wiley-Liss, Inc.
Reactive oxygen species (ROS) are generated as by-products of respiration and are used as signal transducing intermediates in out-in signaling pathways. ROS are also generated during inflammatory responses and it has been shown that hydrogen peroxide may trigger activation of B-lymphocytes, similar to cross-linking of surface immunoglobulins. On the other hand, both exogenous and endogenous generated ROS are a major source of nuclear and mitochondrial DNA (mtDNA) damage. The base excision repair (BER) enzyme APE/Ref-1 normally repairs small nuclear DNA lesion such as oxidized or alkylated bases. It is not clear though whether DNA repair mechanisms able to abolish oxidative damage from nuclear DNA are present into mitochondria too. Here we show by confocal microscopy and Western blot analysis that in the B-lymphocyte Raji cell line a fraction of APE/Ref-1 rapidly re-localizes into mitochondria following H2O2 activation. Targeting of APE/Ref-1 to mitochondria is not associated with cytochrome-c loss or apoptosis induction. These findings indicate that the APE/Ref-1 translocates to mitochondria in response to oxidative stress and thereby it might exert a protective function. (C) 2002 Wiley-Liss, Inc.